A mass spectrometry system is an analytical system used for quantitative and qualitative determination of the compounds of a material (e.g., chemical mixtures and biological samples). In general, a mass spectrometry system uses an ion source to produce electrically charged particles (e.g., molecular or polyatomic ions) from the material to be analyzed. Once produced, the electrically charged particles are introduced to the mass spectrometer and separated by a mass analyzer based on their respective mass-to-charge ratios. The abundance of the separated electrically charged particles are then detected and a mass spectrum of the material is produced. The mass spectrum is analogous to a fingerprint of the sample material being analyzed. The mass spectrum provides information about the mass-to-charge ratio of a particular compound in a mixture sample and, in some cases, molecular structure of that component in the mixture.
The molecular weight of a compound is often determined by the use of a mass spectrometry system having a single mass analyzer. The mass analyzer may include a quadrupole (Q) m ass analyzer, a time-of-flight mass analyzer (TOF-MS), an ion trap mass analyzer (IT-MS), etc. Tandem mass spectrometer s (i.e., tandem-MS or MS/MS) are often needed to analyze samples having complicated molecules. Tandem mass analyzers typically include two mass analyzers of the same or different type (e.g., TOF-TOF MS and Q-TOF MS).
In a tandem mass spectrometry analysis, electrically charged particles are transmitted to the first mass analyzer and an ion of particular interest is selected. The selected ion is transmitted to a dissociation cell where the selected ion is fragmented. The ionic fragments of the dissociated ion are transmitted to the second mass analyzer for mass analysis. The fragmentation pattern obtained from the second mass analyzer is then analyzed to determine the structure of the corresponding molecule.
Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) is of particular importance for the analysis of biological samples, which was introduced by Karas et.al. (Karas, M.; Hillenkamp, F., Anal Chem. 60, p. 2299, 1988) and Tanaka et.al. (Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshica, T., Rapid Commun. Mass Spectrom. 2, p.151, 1988) and has become established as a method of mass spectrometry used to analyze substances such as polypeptides, polynucleotides, proteins, DNA fragments, biopolymers, and other large molecules.
MALDI-MS allows for desorption and ionization of non-volatile samples (e.g., biological samples) from a solid-state phase directly into the gas phase without charring, fragmentation, or chemical degradation. The sample (analyte) is suspended or dissolved in a matrix. Matrices are small organic compounds that are co-crystallized with the analyte.
Laser radiation (i.e., a laser beam) produced by a laser generator, serves as a desorption and ionization source in MALDI-MS. The matrix absorbs the laser energy and causes part of the illuminated sample to vaporize. A rapidly expanding matrix plume carries some of the analyte ions into the vacuum of the mass spectrometer. The matrix molecules absorb most of the incident laser energy minimizing sample damage and ion fragmentation (i.e., soft ionization). Laser generators of various wavelengths (e.g., ultraviolet and infrared) have been used in MALDI-MS.
Conventionally, most laser desorption/ionization sources are performed in a vacuum (vacuum MALDI). In this regard, a sample substrate is under pressure conditions that are similar to the pressure in the mass analyzer (i.e., 1xc3x9710xe2x88x927 Torr). However, MALDI performed at atmospheric pressure (AP-MALDI) (as described in U.S. Pat. No. 5,965,884, which is included herein by reference) has also become available commercially (AP/MALDI(trademark), available from MassTech Inc. of, Burtonsville, Md. is one example). The advantages of AP-MALDI over vacuum MALDI include simple sample handling and reduced analysis time.
Thus, there is a need in the industry for an MALDI-MS system that requires minimal alignment of the laser desorption/ionization source, while also having a high ion throughput. In addition, there is a need in the industry for a MALDI-MS system that can obtain sample ions from different points on a sample surface without having to realign the laser (i.e., profiling a sample), while also having a high ion throughput and being cost effective.
Embodiments of the present invention provide mass spectrometry systems and methods for matrix assisted laser dissociation ionization of a sample. Briefly described, one embodiment of the mass spectrometry system, among others, includes a mass spectrometer having a first end and a second end opposite the first end. In addition, the mass spectrometry system includes a laser generator that produces a laser radiation beam that travels along a first path. Furthermore, the mass spectrometry system includes a sample substrate for holding a sample at the first end of the mass spectrometer. The sample produces a plurality of ions that travels along a second path towards the second end of the mass spectrometer that is substantially parallel the first path.
Other systems, methods, features, and advantages of the present invention will be or become apparent to one with skill in the art upon examination of the following drawings and detailed description. It is intended that all such additional systems, methods, features, and advantages be included within this description, be within the scope of the invention, and be protected by the accompanying claims.